Rapid Access to Chiralα-Alkylated Azacycles via NiH-Catalyzed Asymmetric Migratory Hydroalkylation of N-Heterocyclic Alkenes  

作　　者：Changpeng Chen Wenqing Guo Deyong Qiao Junqian Zhou You Wang Shaolin Zhu 

机构地区：[1]State Key Laboratory of Coordination Chemistry,Jiangsu Key Laboratory of Advanced Organic Materials,Chemistry and Biomedicine Innovation Center(ChemBIC),School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210093 [2]School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang 453007 [3]Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Shanghai Jiao Tong University,Shanghai 200240

出　　处：《CCS Chemistry》2024年第4期898-904,共7页中国化学会会刊（英文）

基　　金：the National Key R&D Program of China(grant no.2022YFA1503200);NSFC(grant nos.92156004,22271146,and 22271143);the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University,the Open Research Fund of the Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,the China Postdoctoral Science Foundation(grant no.2021M701655);the Jiangsu Funding Program for Excellent Postdoctoral Talent(grant no.20220ZB24).

摘　　要：Asymmetric migratory hydrofunctionalization of isomeric mixtures of alkenes provides a complementary approach for the selective introduction of a functional group into a remote C(sp3)-H position.However,the simultaneous control of both regio-and enantioselectivity in this migratory process is a challenge.Enantioenrichedα-alkyl-substituted azacycles are key motifs in pharmaceuticals,natural products,and agrochemicals.Here,we report a NiH-catalyzed asymmetric migratory hydroalkylation process for their efficient and selective construction.In this process,easily available isomeric mixtures of N-heterocyclic alkenes can be directly employed as starting materials,convergently delivering a variety of enantioenrichedα-alkylated azacycles with high levels of regio-and enantioselectivity.The synthetic utility of this transformation is demonstrated by the facile synthesis of two bioactive alkaloids,(+)-connine and(R)-pipecoline.The obtained chiralα-alkylated azacycles also readily undergo diverse derivatization,such as deconstructive halogenation and ring contraction.

关 键 词：ALKENES ALKYLATION asymmetric catalysis ISOMERIZATION nickel 

分 类 号：O62[理学—有机化学]